Curative therapies for sickle cell disease

Abstract

Sickle cell disease (SCD) is an inherited hemoglobinopathy associated with severe morbidity, impaired quality of life, and premature mortality. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment available for patients with SCD and has a >90% event-free survival when a matched related donor is used. However, availability of human leukocyte antigen (HLA)effidentical sibling donors for the SCD population is limited. The use of HLA-matched unrelated donors or related haploidentical donors has the potential to expand the donor pool. Methods: We reviewed the current literature on the indications for SCD transplantation, donor options, and the emerging use of gene therapy as a treatment option. Google Scholar and PubMed were searched using the terms SCD, bone marrow transplantation, donor sources, gene therapy, HSCT, and HLAmatching. Additional articleswere identified fromthe bibliographies of retrieved articles. All articles were reviewed for pertinent information related to SCD and transplantation. Results: HSCT has the potential to establish donor-derived normal erythropoiesis with stable long-term engraftment, amelioration of symptoms, and stabilization of organ damage. The majority of HSCT has been performed in children fromHLA-identical sibling donors and has resulted in excellent rates of survival. The use of alternate donors such as HLA-matched unrelated donors and haploidentical donors has the potential to expand the applicability of HSCT for SCD. Early results in gene therapy for SCD are encouraging.